ObjectiveTo establish a geographical origin identification model for Foeniculi Fructus from Haiyuan， providing a new technical reference for the protection of Haiyuan's geo-authentic medicinal materials and its designation as a national geographical indication agricultural product. MethodsSamples of Foeniculi Fructus were collected from eight producing areas， including Minqin （Gansu）， Bozhou （Anhui）， Qingdao （Shandong）， Dezhou （Shandong）， Urumqi （Xinjiang）， Nujiang （Yunnan）， Gutuo （Inner Mongolia）， and Haiyuan （Ningxia）. Gas chromatography-ion mobility spectrometry （GC-IMS） was used to detect the volatile organic compounds （VOCs） in samples from these geographic origins. VOCs were qualitatively analyzed through dual matching with the National Institute of Standards and Technology （NIST） mass spectral database and the IMS drift time database. Using the Reporter module and Gallery Plot visualization tools within the LAV analytical platform， VOC fingerprint profiles characterizing geographic origins were constructed. A non-targeted analytical strategy was adopted， and 97 VOCs detected via GC-IMS were subjected to principal component analysis （PCA） and partial least squares discriminant analysis （PLS-DA） based on their differential distribution patterns to construct an origin identification model for Foeniculi Fructus from Haiyuan region. Key discriminative markers were screened using variable importance in projection （VIP） values greater than 1. ResultsA total of 97 VOCs were identified， including alcohols， aldehydes， ketones， esters， organic acids， terpenoids， ethers， alkenes， and benzenes. The PLS-DA model， based on VOCs data obtained by GC-IMS， effectively distinguished Foeniculi Fructus in Haiyuan region from those of other origins. During cross-validation， the model achieved a prediction parameter （Q²） of 0.976 and a goodness-of-fit parameter （R²） of 0.936， with no overfitting observed in permutation testing. Twelve key flavor markers with VIP > 1 were identified as characteristic indicators of Haiyuan origin. ConclusionA stable and highly predictive origin identification model for Foeniculi Fructus from Haiyuan was successfully established using GC-IMS technology， PLS-DA， and VIP-based marker screening. This model provides a novel technical strategy for accurately distinguishing Foeniculi Fructus in Haiyuan region from other regional varieties and offers new technical support for its protection as a geo-authentic medicinal material and a nationally designated geographical indication agricultural product in China.

ObjectiveTo establish a geographical origin identification model for Foeniculi Fructus from Haiyuan， providing a new technical reference for the protection of Haiyuan's geo-authentic medicinal materials and its designation as a national geographical indication agricultural product. MethodsSamples of Foeniculi Fructus were collected from eight producing areas， including Minqin （Gansu）， Bozhou （Anhui）， Qingdao （Shandong）， Dezhou （Shandong）， Urumqi （Xinjiang）， Nujiang （Yunnan）， Gutuo （Inner Mongolia）， and Haiyuan （Ningxia）. Gas chromatography-ion mobility spectrometry （GC-IMS） was used to detect the volatile organic compounds （VOCs） in samples from these geographic origins. VOCs were qualitatively analyzed through dual matching with the National Institute of Standards and Technology （NIST） mass spectral database and the IMS drift time database. Using the Reporter module and Gallery Plot visualization tools within the LAV analytical platform， VOC fingerprint profiles characterizing geographic origins were constructed. A non-targeted analytical strategy was adopted， and 97 VOCs detected via GC-IMS were subjected to principal component analysis （PCA） and partial least squares discriminant analysis （PLS-DA） based on their differential distribution patterns to construct an origin identification model for Foeniculi Fructus from Haiyuan region. Key discriminative markers were screened using variable importance in projection （VIP） values greater than 1. ResultsA total of 97 VOCs were identified， including alcohols， aldehydes， ketones， esters， organic acids， terpenoids， ethers， alkenes， and benzenes. The PLS-DA model， based on VOCs data obtained by GC-IMS， effectively distinguished Foeniculi Fructus in Haiyuan region from those of other origins. During cross-validation， the model achieved a prediction parameter （Q²） of 0.976 and a goodness-of-fit parameter （R²） of 0.936， with no overfitting observed in permutation testing. Twelve key flavor markers with VIP > 1 were identified as characteristic indicators of Haiyuan origin. ConclusionA stable and highly predictive origin identification model for Foeniculi Fructus from Haiyuan was successfully established using GC-IMS technology， PLS-DA， and VIP-based marker screening. This model provides a novel technical strategy for accurately distinguishing Foeniculi Fructus in Haiyuan region from other regional varieties and offers new technical support for its protection as a geo-authentic medicinal material and a nationally designated geographical indication agricultural product in China.

This study aimed to comprehensively examine the association of gallstones, cholecystectomy, and cancer risk. Multivariable logistic regressions were performed to estimate the observational associations of gallstones and cholecystectomy with cancer risk, using data from a nationwide cohort involving 239 799 participants. General and gender-specific two-sample Mendelian randomization (MR) analysis was further conducted to assess the causalities of the observed associations. Observationally, a history of gallstones without cholecystectomy was associated with a high risk of stomach cancer (adjusted odds ratio (aOR)=2.54, 95% confidence interval (CI) 1.50-4.28), liver and bile duct cancer (aOR=2.46, 95% CI 1.17-5.16), kidney cancer (aOR=2.04, 95% CI 1.05-3.94), and bladder cancer (aOR=2.23, 95% CI 1.01-5.13) in the general population, as well as cervical cancer (aOR=1.69, 95% CI 1.12-2.56) in women. Moreover, cholecystectomy was associated with high odds of stomach cancer (aOR=2.41, 95% CI 1.29-4.49), colorectal cancer (aOR=1.83, 95% CI 1.18-2.85), and cancer of liver and bile duct (aOR=2.58, 95% CI 1.11-6.02). MR analysis only supported the causal effect of gallstones on stomach, liver and bile duct, kidney, and bladder cancer. This study added evidence to the causal effect of gallstones on stomach, liver and bile duct, kidney, and bladder cancer, highlighting the importance of cancer screening in individuals with gallstones.
Humans ; Mendelian Randomization Analysis ; Gallstones/complications* ; Female ; Male ; Cholecystectomy/statistics & numerical data* ; Middle Aged ; Risk Factors ; Aged ; Adult ; Neoplasms/etiology* ; Stomach Neoplasms/epidemiology*

OBJECTIVE: EPF3 is a fibrinolysin monomer isolated and purified from Pheretima vulgaris Chen, an earthworm used in traditional Chinese medicine as Dilong for treating blood stasis syndrome. Its composition, anticoagulant and fibrinolytic activities, and relevant mechanisms have been confirmed through in vitro experiments. However, whether it has antithrombotic effects in vivo and can be absorbed by the gastrointestinal tract is unknown. This study evaluates the antithrombotic effect in zebrafish and investigates the gastrointestinal stability and intestinal absorption mechanism of this protein in vitro. METHODS: The antithrombotic effect of EPF3 in vivo was verified using the zebrafish thrombus model induced by arachidonic acid and FeCl₃. Then, the protein bands of EPF3 incubated with simulated gastric fluid (SGF), simulated intestinal fluid (SIF), and homogenate of Caco-2 cells (HC2C) were analyzed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis to evaluate its gastrointestinal stability. Finally, the transport behavior and absorption mechanism of EPF3 were studied using Caco-2 cell monolayer. RESULTS: EPF3 could significantly enhance the returned blood volume and blood flow velocity in zebrafish with platelet aggregation thrombus induced by arachidonic acid. It could also prolong the formation time of tail artery thrombus and increase the blood flow velocity in zebrafish with vessel injury thrombus induced by FeCl₃. EPF3 was stable in SIF and HC2C and unstable in SGF. The permeability of EPF3 in Caco-2 monolayer was time-dependent and concentration-dependent. The efflux ratio was less than 1.2 during transport, and the transport behavior was not affected by inhibitors. EPF3 could reversibly reduce the expression of tight junction-related proteins, including zonula occludens-1, occludin, and claudin-1 in Caco-2 cells. CONCLUSION EPF3 could play a thrombolytic and antithrombotic role in zebrafish. It could be transported and absorbed into the intestine through cellular bypass pathway by opening the intestinal epithelium tight junction. This study provides a scientific explanation for the antithrombotic effect of earthworm and provides a basis for the feasibility of subsequent development of EPF3 as an antithrombotic enteric-soluble preparation. Please cite this article as: Zhong WL, Yang JQ, Liu H, Wu YL, Shen HJ, Li PY, Du SY. Antithrombotic effect in zebrafish of a fibrinolytic protein EPF3 from Dilong (Pheretima vulgaris Chen) and its transport mechanism in Caco-2 monolayer through cell bypass pathway. J Integr Med. 2025; 23(4): 415-428.
Animals ; Zebrafish ; Humans ; Caco-2 Cells ; Fibrinolytic Agents/pharmacology* ; Thrombosis/drug therapy* ; Intestinal Absorption

ObjectiveTo understand the incidence and death of female breast cancer patients and the premature death caused by breast cancer in Putuo District of Shanghai， and to reduce the incidence of breast cancer， mortality and the probability of early death， and to provide reference for realizing the control target of the probability of early death of major chronic diseases. MethodsThe incidence and death data of the registered female residents with breast cancer in Putuo District of Shanghai from 2004 to 2019 were collected using Shanghai Population-based tumor registration management system. The crude incidence rate， standardized incidence rate， crude mortality rate， standardized mortality rate， age-specific incidence rate， age-specific mortality rate and other indicators were calculated. The Joinpoint regression model was used to calculate the annual percentage change （APC） and average annual percentage change （AAPC） of breast cancer incidence， mortality and premature death probability， and to analyze the changing trend. ResultsFrom 2004 to 2019， the crude incidence of breast cancer in Putuo District of Shanghai increased from 75.76/10⁵ to 95.77/10⁵ （APC=2.26%， t=6.05， P<0.01）， while the standardized incidence did not decrease significantly during 2004‒2008 （APC=-4.83%， t=-1.81， P=0.10） and showed an upward trend after 2008 （APC=1.67%， t=2.84， P=0.02）. The crude mortality rate changed from 18.52 per 10⁵ to 21.63 per 10⁵ （APC= 1.51%， t=1.52， P=0.15）， and the standardized mortality rate decreased from 9.91/10⁵ to 7.44/10⁵ （APC=-1.46%， t=-2.43， P=0.03）. The incidence rate in the group of 30‒69 years increased from 98.39/10⁵ to 111.75/10⁵ （APC=1.14%， t=3.05， P=0.01）， and the mortality rate increased from 16.13/10⁵ to 19.30/10⁵ （APC=0.48%， t=0.84， P=0.41）. The incidence rate of patients aged ≥70 years varied from 165.68/10⁵ to 139.53/10⁵ （APC=1.54%， t=1.25， P=0.23）， and the mortality rate changed from 85.08/10⁵ to 56.64/10⁵ （APC=-0.18%， t=-0.08， P=0.94）. The probability of premature death from breast cancer decreased from 7.73‰ to 6.61‰ （APC=-1.56%， t=-2.30， P=0.04）. ConclusionThe risk of female breast cancer morbidity and death can not be ignored， and the control pressure of premature death probability is still large. Attention should be paid to the age group of 30‒69 years old， and further measures should be taken to control the increase of incidence and to reduce mortality， so as to reduce the probability of premature death of female breast cancer， and promote the realization of the overall control goal of premature death probability.

OBJECTIVE To screen the prescription and preparation method of Bupleurum nanoemulsion, and evaluate its quality, study the antipyretic effect. METHODS The emulsifier and co-emulsifier of the nanoemulsion were preliminarily screened, and then the prescription was screened by pseudo-ternary phase diagram. The quality evaluation of the appearance, particle size distribution, structure type, stability and content of the prepared Bupleurum nanoemulsion was performed. Wistar rats were further randomly divided into blank control group, model control group, positive control group(aspirin group), Bupleurum nanoemulsion high-dose, medium-dose and low-dose groups(18.00, 9.00, 3.00 g·kg−1). Except for the blank control group, the pathological model of fever rats was prepared in the other groups. According to the scheduled experimental requirements, rats in each group were given the corresponding drugs. And the temperature changes of rats in each group were recorded at 0.5, 1, 1.5, 2, 3 h to observe the antipyretic effect of Bupleurum nanoemulsion. RESULTS The best prescription of Bupleurum nanoemulsion: Tween-80 6 g and n-butanol 3 g, Bupleurum extract dissolved in pure water as water phase 20 mL, Bupleurum oil as oil phase 2 g. At room temperature, the Bupleurum nanoemulsion was a yellow-brown clear and transparent liquid, O/W nanoemulsion, with an average particle size of (77.21±3.66)nm, polydispersity index of 0.28±0.04, Zeta potential of (–18.81±1.42)mV, and saikosaponin content of 3.071 mg·mL−1, with good stability. In animal experiments, compared with the model control group, the rectal temperature of aspirin group and Bupleurum nanoemulsion high-dose group was significantly lower after the first administration(P<0.01), the rectal temperature of Bupleurum nanoemulsion middle-dose group was significantly lower after the first administration 2, 3 h(P<0.01). CONCLUSION The Bupleurum nanoemulsion is transparent and stable, and it has good antipyretic effect on fever rat model.

Objective To investigate the acupoint selection rules of obesity complicated with type 2 diabetes mellitus(T2DM)through R language data mining technology.Methods CNKI,Wanfang,VIP,CBM,PubMed,Embase,Cochrane Library,web of science and other major databases were searched by computer.From the establishment of the database to January 2024,the clinical research literature on acupuncture and moxibustion for the treatment of obesity with T2DM was included.Microsoft Excel 2021 was used to establish a database of acupoint prescriptions.R 4.3.2 and Rstudio software were used to analyze the frequency,meridian tropism,specific acupoints,correlation analysis,association rules and cluster analysis of acupoints.Results A total of 81 articles were included,and 117 prescriptions were extracted.It involves 82 acupoints,and the total frequency of acupoint usage is 1 072 times.The top five acupoints with the highest frequency were Zusanli(ST36),Zhongwan(RN12),Weiwanxiashu(EX-B3),Pishu(BL20),Tianshu(ST25).The meridian selection is mainly based on the stomach meridian of foot yangming,ren meridian,foot taiyang bladder meridian and foot taiyin spleen meridian.The five-shu points are the specific points with the highest frequency of use.Correlation analysis showed that there were three groups of strongly related acupoint groups.The core acupoints were obtained by association rule analysis.Cluster analysis and machine voting were performed on acupoints with frequency ≥ 10 by function,and a total of four cluster acupoint groups were obtained.Conclusion Through R language data analysis,the principle of acupoint selection for acupuncture and moxibustion in the treatment of obesity complicated with T2DM is mainly based on abdominal local acupoints,combined with visceral syndrome differentiation and empirical point selection,which provides effective treatment ideas for acupuncture and moxibustion in the treatment of obesity complicated with T2DM.

OBJECTIVE To investigate the current situation of pharmaceutical clinic service in medical institutions in China and provide experience and suggestions for promoting the development of pharmaceutical clinics. METHODS Questionnaire survey was used to investigate the development of pharmaceutical clinics in medical institutions of 31 provinces （autonomous regions and municipalities directly under the central government） in March to April 2023， and the descriptive analysis was conducted. The regression analysis was carried out for the influential factors of pharmaceutical clinic service. RESULTS A total of 1 368 questionnaires were distributed in this survey and 1 304 valid questionnaires were collected with the effective response rate of 95.32%. A total of 463 medical institutions carried out pharmaceutical clinic service， the rate of which was 35.51% （463/1 304）； the rates of pharmaceutical clinics in tertiary， secondary， primary and other medical institutions were 52.80%， 17.18% and 5.88%， respectively. The frequency of opening pharmaceutical clinics was 3.17 days per week on average， with an average of 5.99 visiting pharmacists in each medical institution. Among the visiting pharmacists， clinical pharmacists accounted for the vast majority （88.68%， 2 459/2 773）. There were various categories of pharmaceutical clinics， including joint clinics and pharmacist-independent clinics； among pharmacist-independent clinics， pharmaceutical specialty/specialty disease clinics were the main ones， accounting for 89.72% of the total number of pharmaceutical clinics. The value of pharmacists in pharmaceutical clinics was manifested in various forms， among which the proportion of medical institutions charging pharmaceutical clinics was 10.80%. The main experiences in developing pharmaceutical clinics were to attach importance to discipline construction and personnel training. The main difficulties in developing pharmaceutical clinics were low compensation levels and a shortage of talent.The number of clinical pharmacists， the number of visiting pharmacists in pharmaceutical clinics and additional compensation were positively correlated with the amount of pharmaceutical clinic services（P＜0.05）. CONCLUSIONS In recent years， pharmaceutical clinics have made significant progress； in the future， it is still necessary to further strengthen discipline construction and talent cultivation， pay attention to the value embodiment of pharmacists， to promote the healthy development of pharmaceutical clinics.

Objective To explore the effectiveness of high-definition diffusion weighted imaging(DWI)sequence combined with T1 WI-fat suppression(FS)dynamic contrast enhancement(DCE)sequence for preoperative T-stage of rectal cancer by using 3.0T MRI standardized scanning.Methods A retrospective analysis was conducted on MRI images of 57 patients with rectal cancer confirmed by pathology.Before surgery,the patients underwent 3.0T MRI standardized rectal cancer scan methods,including routine sequence,high-definition DWI sequence,and T1 WI-FS DCE sequence,etc.Then two experienced physicians evaluated the T-stage of preoperative rectal cancer through high-definition DWI(transverse and sagittal sections)and T1 WI-FS DCE sequences in the double-blind method.Using the postoperative pathological results of rectal cancer as the"gold standard",two sequences were combined to evaluate the accuracy,sensitivity,and specificity of rectal cancer T-stage.Results Among the 57 cases,there were 9 cases of upper rectal cancer,39 cases of middle rectal cancer,and 9 cases of lower rectal cancer.The accuracy rates of preoperative T-stage diagnosis for rectal cancer by two evaluator were both 85.7％(6/7)in T1 stage,88.2％(15/17)and 94.1％(16/17)in T2 stage,96.9％(31/32)and 93.8％(30/32)in T3 stage,and both 100.0％(1/1)in T4 stage.For evaluator 1,the sensitivity and specificity of the rectal cancer T-stage diagnosis were 96.1％and 83.3％,and for evaluator 2 were 94.1％and 83.3％,respectively.For rectal cancer MRI diagnosis,the accuracy rates and sensitivity were higher when combining the high-definition DWI sequence and T1 WI-FS DCE sequence,compared with a single high-definition DWI sequence or T1 WI-FS DCE sequence,and the difference was statistically significant.The average preoperative apparent diffusion coefficient(ADC)value of rectal cancer was compared between the corresponding postoperative pathological T1 to T4 stage groups,and the difference was statistically significant.Conclusion The combination of high-definition DWI sequence and T1 WI-FS DCE sequence improves the accuracy of rectal cancer T-stage,providing assistance for personalized clinical treatment.

Lipophosphatidic acid(LTA)was used to stimulate Mac-T cells,and the expression lev-els and phosphorylation levels of key proteins of nuclear factor-κB(NF-κB)and mitogen-activated protein kinase(MAPK)signaling pathway and the expression levels of upstream key action factors TLR4 and MyD88 proteins were detected by Western blot,and EDU assay was used to detect cell proliferation levels and flow cytometry was used to detect apoptosis.The results showed that acti-vation of GPR120 significantly decreased the phosphorylation levels of LTA-induced NF-κB(P65 and IκBα)(P＜0.01)and MAPK(JNK,ERK,p38)(P＜0.01)in Mac-T cells;inhibition of GPR120 was able to upregulate LTA-induced NF-κB(p65 and IκBα)in Mac-T cells(P＜0.01)and MAPK(JNK,ERK,p38)phosphorylation levels(P＜0.01);and activation of GPR120 significantly allevia-ted LTA-induced upregulation of TLR4 and MyD88(P＜0.01);inhibition of GPR120 significantly exacerbated LTA-induced upregulation of TLR4 and MyD88(P＜0.05);LTA stimulation led to a trend of diminished Mac-T cell proliferation and significantly increased apoptosis,whereas activa-tion of the GPR120 gene significantly increased cell activity(P＜0.01),promoted cell proliferation and significantly reduced apoptosis(P＜0.05)thereby alleviating the damage to Mac-T cells by LTA;LTA stimulation led to a highly significant increase in apoptosis(P＜0.01).In contrast,acti-vation of the GPR120 gene significantly reversed the increase in the apoptosis rate of Mac-T cells induced by LTA(P＜0.01),while inhibition of the GPR120 gene enhanced the apoptosis-promo-ting effect of LTA(P＜0.05),indicating that activation of the GPR120 gene attenuated the in-crease of apoptosis rate caused by LTA-induced inflammatory Mac-T cells.The results suggest that GPR120 can regulate inflammation by mediating TLR4 and MyD88 expression to inhibit NF-κB/MAPK inflammatory pathway activation and can promote cell proliferation.